Heretofore, in methods for controlling release of a substance of interest carried in a molecular assembly such as liposome, pH responsiveness has been widely used. In this regard, “pH responsiveness” refers to characteristics of a molecular assembly in which the molecular packing state, property of releasing a substance carried and the like are changed in response to changes in pH. In particular, pH-responsive liposome using phosphatidylethanolamine-type phospholipid is well known (for example, see: D. Papahadjopoulos et al., Biochemistry, 24 (1985) 3091-3098; and D. H. Thompson et al., Langmuir, 19 (2003) 6408-6415). This utilizes the property of phosphatidylethanolamine-type phospholipid in which structural transition thereof occurs in response to pH to change the molecular packing state of a liposome bilayer membrane. However, such structural transition does not easily occur in the presence of serum. Therefore, it is not practical for use in vivo.
In addition, as pH-responsive liposome, liposome in which anionic lipid and cationic lipid are mixed together is known (see G Shi et al., Journal of Controlled Release 80 (2002) 309-319). However, since it is required to combine anionic lipid and cationic lipid, it is difficult to adjust pH responsiveness depending on purposes. Moreover, cationic lipid itself has low retentivity in blood and high cytotoxicity. Furthermore, only cationic lipid can be fused with an anionic biomembrane at low pH. Therefore, there is a problem with low degree of fusion of liposome.